Targeted cloning of cytotoxic T cells specific for minor histocompatibility antigens restricted by HLA class I molecules of interest1

Akatsuka, Yoshiki; Kondo, Eisei; Taji, Hirohumi; Morishima, Yasuo; Yazaki, Makoto; Obata, Yuichi; Kodera, Yoshihisa; Riddell, Stanley R.; Takahashi, Toshitada

doi:10.1097/00007890-200212270-00023

Cited by 10 publications

(9 citation statements)

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“…The culture media consisted of RPMI-HEPES (GIBCO BRL) containing 10% pooled, heatinactivated human serum, and IL-2 (50 U/ml; Chiron Corp.). The T cell clone was used in cytotoxicity and epitope reconstitution assays either 12-16 d after stimulation (19), or 1 d after thawing a frozen aliquot. B-LCL were maintained in RPMI-HEPES with 10% FBS (ATLAS Biologicals).…”

Section: Methodsmentioning

confidence: 99%

A Human Minor Histocompatibility Antigen Resulting from Differential Expression due to a Gene Deletion

Murata

Warren

Riddell

2003

The Journal of Experimental Medicine

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155

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Minor histocompatibility antigens (minor H antigens) are targets of graft-versus-host disease and graft-versus-leukemia responses after allogeneic human leukocyte antigen identical hematopoietic stem cell transplantation. Only a few human minor H antigens have been molecularly characterized and in all cases, amino acid differences between homologous donor and recipient proteins due to nucleotide polymorphisms in the respective genes were responsible for immunogenicity. Here, we have used cDNA expression cloning to identify a novel human minor H antigen encoded by UGT2B17, an autosomal gene in the multigene UDP-glycosyltransferase 2 family that is selectively expressed in liver, intestine, and antigen-presenting cells. In contrast to previously defined human minor H antigens, UGT2B17 is immunogenic because of differential expression of the protein in donor and recipient cells as a consequence of a homozygous gene deletion in the donor. Deletion of individual members of large gene families is a common form of genetic variation in the population and our results provide the first evidence that differential protein expression as a consequence of gene deletion is a mechanism for generating minor H antigens in humans.

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Section: Methodsmentioning

confidence: 99%

A Human Minor Histocompatibility Antigen Resulting from Differential Expression due to a Gene Deletion

Murata

Warren

Riddell

2003

The Journal of Experimental Medicine

Self Cite

183

155

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“…( 30 ) CTL clones were generated from post‐HCT peripheral blood of two independent patients with advanced leukemia using a CTL cloning method targeting HLA alleles of interest the authors developed. ( 38 ) To map gene(s) encoding mHag recognized by these CTL, a panel of B lymphoid cell lines (B‐LCL) registered to the Center d’Etude du Polymorphisme Humain (CEPH) foundation was screened after transfecting restriction HLA alleles using an efficient retrovirus system. ( 39 ) The CEPH cell lines comprise B‐LCL from large families, individuals of which have been genetically mapped.…”

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confidence: 99%

Minor histocompatibility antigens as targets for immunotherapy using allogeneic immune reactions

et al. 2007

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Minor histocompatibility antigens (mHag) were originally identified as antigens causing graft rejection or graft-versus-host disease in human leukocyte antigen (HLA)-matched allogeneic transplantation. Molecular identification has revealed most to be major histocompatibility complex (MHC)-bound short peptide fragments encoded by genes which are polymorphic due to single nucleotide polymorphisms (SNP). Genotypic disparity of SNP between transplantation donors and recipients gives rise to mHag as non-self antigens for both the donor and the recipient. Subsequently, mHag have been explored as immunotherapeutic antigens for use against recurring hematological malignancies after allogeneic hematopoietic cell transplantation (HCT), because mHag expressed only on hematopoietic cells are considered to augment graft-versusleukemia/lymphoma (GVL) effects without increasing the risk of life-threatening graft-versus-host disease (GVHD). Accumulating evidence suggests that T-cell responses to mHag aberrantly expressed on solid tumor cells are also involved in the eradication of sensitive tumors such as renal cell carcinomas following HCT. Over the past decade, the number of putative GVL-directed mHag has increased to a level that covers more than 30% of the Japanese patient population, so that clinical trials may now be executed in the setting of either vaccination or adoptive immunotherapy. As it is expected that immune responses to alloantigens are more powerful than to tumor antigens mostly derived from overexpressed selfproteins, mHag-based immunotherapy may lead to a new treatment modality for high-risk malignancies following allogeneic HCT.

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“…mHAgs or other non-MHC D/R responses in transplant recipients other than the generation of specific T-cell clones in vitro. A few isolated reports have demonstrated the feasibility of applying a modified MLR reaction that uses mDC as stimulators [18,19]; the trans vivo DTH [20], and CTL [21] have also been used. In this study, we have utilized the unique capacity of mDC to primarily stimulate lymphocytes in an energy consumption (and lymphoproliferation) assay in HLAgi sibling volunteers and in HLAgi sibling D/R pairs pre-and post-transplant.…”

Section: Discussionmentioning

confidence: 99%

A Novel Approach to Detect Donor/Recipent Immune Responses Between HLA-Identical Pairs

et al. 2007

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Targeted cloning of cytotoxic T cells specific for minor histocompatibility antigens restricted by HLA class I molecules of interest1

Cited by 10 publications

References 0 publications

A Human Minor Histocompatibility Antigen Resulting from Differential Expression due to a Gene Deletion

A Human Minor Histocompatibility Antigen Resulting from Differential Expression due to a Gene Deletion

Minor histocompatibility antigens as targets for immunotherapy using allogeneic immune reactions

A Novel Approach to Detect Donor/Recipent Immune Responses Between HLA-Identical Pairs

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